When should I routinely order a Thyroid-Stimulating Hormone (TSH) receptor antibody (Ab) test?

Indications for TSH Receptor Antibody Testing

TSH receptor antibody (TRAb) testing should be ordered when evaluating patients with hyperthyroidism to distinguish between Graves' disease and other causes of thyrotoxicosis, particularly when the diagnosis is unclear from clinical presentation alone.

Primary Indications for TRAb Testing

• Differential diagnosis of hyperthyroidism

  • When clinical features and initial thyroid function tests suggest hyperthyroidism (low TSH with elevated T4/T3)
  • To distinguish Graves' disease from other causes of thyrotoxicosis (thyroiditis, toxic nodular goiter) 1, 2
  • When the clinical diagnosis is uncertain (sensitivity of clinical diagnosis alone is only 88% with 34% false positive rate) 2

• Pregnancy-related indications

  • In pregnant women with current or previous Graves' disease
  • Particularly when TRAb levels ≥5 IU/L, as this indicates increased risk of fetal and neonatal thyrotoxicosis 3
  • When planning pregnancy in women with a history of Graves' disease

• Treatment decision-making

  • To guide treatment choice between antithyroid drugs, radioactive iodine, or surgery 3
  • When predicting risk of relapse after antithyroid drug therapy
    • TRAb >12 IU/L at diagnosis indicates 60% risk of relapse at 2 years
    • TRAb >7.5 IU/L at 12 months or >3.85 IU/L at cessation of therapy indicates >90% risk of relapse 3

• Monitoring disease activity

  • During antithyroid drug treatment to assess response and predict remission 4
  • After radioactive iodine therapy (levels typically increase for a year, then gradually fall) 3
  • In patients with Graves' ophthalmopathy, as TRAb levels parallel the course of eye disease 3

Special Populations Requiring TRAb Testing

• Children and adolescents with type 1 diabetes who develop thyroid dysfunction 5
• Patients with autoimmune disorders who develop symptoms of hyperthyroidism
• Patients with atrial fibrillation of unclear etiology
• Women with unexplained infertility or recurrent pregnancy loss

Clinical Value and Test Performance

• Modern TRAb assays (2nd and 3rd generation) have excellent diagnostic performance:
  • Sensitivity: 97.1-98.3%
  • Specificity: 97.4-99.2% 6
  • Likelihood of a TRAb-positive individual having Graves' disease is 1367-3420 times greater than a TRAb-negative person 6

When Not to Order TRAb Testing

• Routine thyroid screening in asymptomatic individuals 5
• Patients with overt hypothyroidism
• Monitoring of levothyroxine replacement therapy in hypothyroidism
• Follow-up of treated Graves' disease patients who have achieved stable remission

Common Pitfalls to Avoid

• Relying solely on clinical diagnosis without TRAb testing can lead to misdiagnosis in up to 34% of cases 2
• Failing to test TRAb in pregnant women with current or previous Graves' disease
• Not considering TRAb testing in patients with subclinical hyperthyroidism who may have early Graves' disease
• Overlooking the need for TRAb testing in patients with thyroid eye disease even with normal thyroid function tests

By following these guidelines for appropriate TRAb testing, clinicians can improve diagnostic accuracy, guide treatment decisions, and optimize outcomes for patients with suspected or confirmed Graves' disease.